Aerobic glycolysis activation through canonical WNT/β-catenin pathway in ALS

Energy is the major determinant of neuronal viability. We focus our synthesis on the hypothesis of the development of aerobic glycolysis by the stimulation of the canonical WNT/beta-catenin pathway in amyotrophic lateral sclerosis (ALS). The stimulation of the canonical WNT/beta-catenin pathway induces the activation of aerobic glycolysis, also called Warburg effect, via the stimulation of glycolytic enzymes such as Glut (glucose transporter), PKM2 (pyruvate kinase M2), PDK1 (pyruvate dehydrogenase kinase 1), LDH-A (lactate dehydrogenase A) and MCT-1 (monocarboxylate transporter 1). The aerobic glycolysis consists to a supply of a large part of glucose into lactate regardless of oxygen. Aerobic glycolysis is less efficient in terms of ATP production than oxidative phosphorylation due to the shunt of the TCA cycle. Dysregulation of cellular energy metabolism promotes cell death and participates to the progression of ALS. Controlling the expression of the canonical WNT/beta-catenin signaling pathway is an attractive strategy to regulate aerobic glycolysis initiation and the progression of ALS.